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Biomedical subjects

J Webb

Publications and source records attributed to J Webb.

At least 55 records · Page 3Linked to original sources

Anti-Sm and anti-DNA antibodies in paired serum and synovial fluid samples from patients with SLE.

Antibodies to nuclear antigens (ANAs) are frequently found in the serum of patients with connective tissue diseases (CTDs). Particularly systemic lupus erythematosus (SLE), and have been implicated in the immune-complex mediated pathogenesis of these diseases. In this study we have compared the occurrence of precipitating ANAs in paired samples of serum and synovial fluid from patients with different CTDs. Of the 30 patients examined 3 had precipitating ANAs in their serum only, 1 in the synovial fluid only, and 3 had antibodies in both serum and synovial fluid. Precipitating ANAs in synovial fluid were found in 3/6 patients with SLE, 1 patient with RA/Sjogren's syndrome overlap, and one patient with RA/SLE overlap. Of the other 15 patients with RA, 2 had precipitating antibodies only in their serum. Two of the SLE patients had anti-Sm antibody, one in serum only and the other in both serum and synovial fluid. Detection by ELISA of class specific anti-Sm antibodies in serum or synovial fluid paralleled the occurrence of antidenatured DNA antibodies when both specificities occurred together. One SLE patient did show evidence in synovial fluids of elevated concentrations of specific antibody classes to individual antigens; however, elevated levels were more frequently found in serum. Local production of ANAs does not, therefore, appear to be a feature of synovial fluids from SLE patients.

Antibodies

Benign joint hypermobility with neuropathies: documentation and mechanism of median, sciatic, and common peroneal nerve compression.

We report three patients in whom carpal tunnel syndrome was due to neurapraxis as a consequence of unusual sleep postures enabled by their benign joint hypermobility syndrome (BJHS). A fourth patient also had bilateral sensory sciatic neuropathy and a common peroneal palsy, similarly due to regularly adopted unusual postures. Recognition of such cause-effect mechanisms and their simple solution in BJHS should obviate needless investigation and unnecessary surgery.

Adult

Geographical variation in the incidence of diabetes mellitus in Scottish children during the period 1977-1983.

Routinely collected Scottish hospital discharge data were used to identify newly diagnosed cases of diabetes mellitus under the age of 19 years. In the period 1977-83 there were 2183 cases, an average annual incidence of 21.0 per 100,000 per annum. This rate is one of the highest reported and represents a continuation of the increase in incidence which occurred during the period 1968-76. Statistically significant geographical variation in incidence was observed with the higher incidence in the least densely populated areas. Seasonal variation in the month of first admission was evident in all except the under-five age group with peaks occurring in winter. An estimated 60% of newly diagnosed cases were readmitted within 5 years and the pattern of readmission was found to differ little between males and females or between age groups.

Adolescent

Improved detection of anti-Jo-1 antibody, a marker for myositis, using purified histidyl-tRNA synthetase.

The increased detection of anti-Jo-1 antibody afforded by the use of the purified antigen, histidyl-tRNA synthetase, in counterimmunoelectrophoresis is demonstrated. Using purified antigen, anti-Jo-1 antibody was detected in the sera of 16/33 (48.5%) patients with confirmed myositis and in 20/45 (44.5%) patients with confirmed or possible myositis. This rate is approximately double that obtained with commercial thymus extracts both in this study and seven others reported in the literature. The presence of antibody shows marked correlation with the activity of myositis at the time of serum sampling and with the presence of interstitial lung disease. Detection rates are similar in patients with polymyositis and dermatomyositis both with and without additional connective tissue diseases.

Adult

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Animals

Hydatidiform mole in England and Wales 1973-83.

The number of cases of hydatidiform mole (HM) registered annually in England and Wales has risen since 1973 to 1.54 per 1000 live births in 1983. For women over 50 the risk per pregnancy was 411 times and for girls under 15 it was six times greater than that for women aged 25-29. 7.75% of patients had chemotherapy for invasive mole or choriocarcinoma. Patients who had had oxytocin-induced or prostaglandin-induced uterine evacuation or hysterotomy were more likely to need chemotherapy. Human chorionic gonadotropin (HCG) was undetectable by 56 days after evacuation in 42% of patients, none of whom required chemotherapy; a considerable reduction in follow-up time for this subgroup is proposed. For patients whose HCG values became normal more than 56 days after evacuation and stayed normal for 6 months the risk of recrudescent disease was 1 in 286. In subsequent pregnancies the risk of a second HM was 1 in 76 and that of a third was 1 in 6.5. 11 (0.2%) patients died, 2 from drug-resistant choriocarcinoma.

Adolescent

Mössbauer spectroscopic studies of the cores of human, limpet and bacterial ferritins.

Ferritin cores from human spleen, limpet (Patella vulgata) haemolymph and bacterial (Pseudomonas aeruginosa) cells have been investigated using 57Fe Mössbauer spectroscopy. The Mössbauer spectra were recorded over a range of temperatures from 1.3 to 78 K, all the spectra are quadrupole-split doublets with similar quadrupole splittings and isomer shifts, characteristic of iron(III), while at sufficiently low temperatures the spectra of all the samples show well-resolved magnetic splitting. At intermediate temperatures, the spectra from the human ferritin exhibit typical superparamagnetic behaviour, while those from the bacterial ferritin show behaviour corresponding to a transition from a magnetically ordered to a paramagnetic state. The spectra from the limpet ferritin show a complex combination of the two effects. The results are discussed in terms of the magnetic behaviour of small particles. The data are consistent with magnetic ordering temperatures of about 3 and 30 K for the bacterial and limpet ferritin cores, respectively, while the data indicate that the magnetic ordering temperature for the human ferritin cores must be above 50 K. These differences are interpreted as being related to different densities of iron in the cores and to variations in the composition of the cores. The human ferritin cores are observed to have a mean superparamagnetic blocking temperature of about 40 K, while that of the limpet ferritin cores is about 25 K. This difference is interpreted as being due not only to different mean numbers of iron atoms in the two types of core but also to the higher degree of crystallinity in the cores of the human ferritin.

Animals

Complement and immune complex diseases.

Research during the past decade has led to a much greater understanding of the activation and control, as well as a more complete delineation, of the complement system of proteins. There has been definition of the roles of individual components in modulation of immune complex formation, the deposition of which leads to tissue injury in the autoimmune connective tissue diseases. The ability of serum to render immune complexes more soluble is complement-mediated and appears to be an important protective mechanism against immune complex diseases. Inherited deficiencies and production of non-functional variants of complement components, decreased synthesis, hypercatabolism, and the presence of serum inhibitors may all contribute to the reduced immune complex solubilisation which has been found in the connective tissue diseases. More work is required to define further the role of complement and immune complexes in the basic pathogenesis of these diseases.

Antigen-Antibody Complex

Autonomic regulation of postprandial plasma somatostatin, gastrin, and insulin.

To evaluate the neural regulation of postprandial somatostatin release we studied the effect of blockade of (a) alpha-adrenergic and beta-adrenergic and (b) cholinergic receptors on the plasma somatostatin, gastrin and insulin responses to a standard meal in two groups of five fasting healthy male volunteers. Thymoxamine (0.1 mg/kg iv over two minutes then 10 mg/hour for two hours) and propranolol (0.15 mg/kg iv over two minutes, then 0.75 mg/kg/hour for two hours) were started just before eating while atropine (0.04 mg/kg/im) was given at 15 minutes on completion of the meal. There was a prompt and sustained rise in plasma somatostatin after a control meal in all experiments. This rise was arrested by atropine but not altered by either thymoxamine or propranolol. The plasma gastrin response to a meal was moderately enhanced by thymoxamine and markedly enhanced by atropine. Postprandial insulin release was not affected by alpha- or beta-adrenergic blockade but was abolished by atropine. The effect of atropine on the postprandial plasma somatostatin rise might have been mediated through reduction in gastric acidity or delay in gastric emptying. Hence we gave five fasting male volunteers and intraduodenal infusion of fat emulsion (25 calories in 30 minutes) on two occasions both alone and after atropine. Plasma somatostatin rose during the fat infusion alone and this rise was abolished by atropine. These data suggest that (a) cholinergic but not adrenergic mechanisms are important modulators of plasma somatostatin release after orally ingested and intraduodenally infused nutrients (b) atropine abolishes plasma somatostatin release independently of its effects on gastric acidity and motility and (c) are consistent with the hypothesis that atropine potentiates postprandial gastrin release through reduction of somatostatin mediated inhibition.

Adult

In vivo anti-nuclear antibodies in epithelial biopsies in SLE and other connective tissue diseases.

In vivo anti-nuclear antibody (ANA) was observed by direct immunofluorescence microscopy in epithelial cell nuclei in forty-four biopsies from thirty-three patients. The tissue containing the ANA was macroscopically normal in twenty-seven patients. The thirty-three patients with in vivo biopsy ANA included twenty-three with SLE, three with mixed connective tissue disease, two each with multi-system Sjögren's syndrome, dermatomyositis, and progressive systemic sclerosis, and one with rheumatoid arthritis. Features of sicca syndrome were noted in seventeen patients. The patterns of the in vivo biopsy ANA in the thirty-three patients were speckled (21), homogeneous (6), nodular (2), and both speckled and homogeneous (4). Complement was not detected in the epithelial cell nuclei. Immunoglobulin(s) and/or complement were deposited along the dermoepidermal junction in thirty-two of the forty-four biopsies, and in dermal blood vessels in twenty-two biopsies. Each patient had serum ANA against rat liver substrate; twenty-seven had high titre ANA (1 in 1000 or greater). Elevated levels of DNA-binding were found in twenty patients (61%), but the level of DNA-binding did not correlate with the intensity of in vitro biopsy ANA staining. Serum antibody to ribonucleoprotein (RNP) was present in eight of the twenty-three patients tested (35%), all eight patients having clinical features of sicca syndrome. Hypocomplementaemia was found in thirteen patients (40%), all of whom had active SLE. In vivo biopsy ANA appears to be a real phenomenon of unknown aetiology, and not an artifact, which is found in some patients with active multisystem autoimmune disease, especially SLE.

Adult

Plasmacytoma of the stomach: diagnosis with the aid of immunoperoxidase technique.

A gastric tumor, originally diagnosed as a plamacytoma in 1953, but in which the diagnosis was disputed, has been re-examined by the immunoperoxidase staining technique. The demonstration of a single type of immunoglobulin in the tumor cells is considered conclusive evidence of its neoplastic nature. Two further cases of gastrict plasmacytoma encountered in recent months have also been examined by this technique and similar results obtained. The pathology of plasma cell tumors is discussed and a brief review of the literature is added with regard to the management and the overall poor prognosis.

Clone Cells

Severe hypercapnia associated with a non-respiratory alkalosis.

A case of hypoventilation in response to a non-respiratory alkalosis is presented. It is postulated that the degree of hypoventilation encountered was a normal response and that a fall in intracellular hydrogen ion concentration was responsible for the hypoventilation. This explains why the alkalosis associated with potassium deficiency is not associated with hypoventilation since the intracellular hydrogen ion concentration then remains constant. The renal response in this condition is responsible for maintaining the alkalosis and seems to be aimed at sodium conservation and hence plasma volume control rather than defence of acid-base balance.

Alkalosis

Clinico-laboratory aspects of anti-nuclear and anti-native DNA antibody tests.

Available techniques for detection of anti-nuclear antibodies are here briefly reviewed. The relatively insensitive LE cell test has been largely supplanted by the indirect immunofluorescent ANA test which should be reported in terms of titre and pattern. Specific measurement of nDNA antibodies is now a regular technique in SLE diagnosis and management.

Antibodies, Antinuclear

Crystal induced arthritis: gout and pseudogout.

Intrasynovial deposits of monourate crystals in the presence of serum hyperuricaemia, and calcium pyrophosphate dihydrate (CPPD) crystals, are responsible for gout and pseudogout respectively. Identification of these by synovial fluid analysis is described. The clinical features, minimum investigations, history-taking, management and drug regimes of gout and pseudogout are discussed. Periodic review of the patient is stressed. Other intrasynovial crystals are briefly outlined.

Acute Disease